A predisposition developing dermatitis, asthma, or hay fever in response to specific foods and respiratory exposure to specific substance was first described as “atopy” by Coca in 1925. Atopic diseases include asthma, allergic rhinitis, allergic conjunctivitis and atopic dermatitis, etc. The incidence of atopic dermatitis has rapidly increased in worldwide due to increased environmental pollutants. The prevalence of atopic disease reaches 20% of normal individuals in worldwide. The quality of lives of patients having atopic dermatitis is very poor since their daily lives are constrained and affected by the symptoms. The financial burden of the society for the prevention and treatment of atopic dermatitis has also increased drastically. Accordingly, the development of effective medicines to manage or treat atopic diseases is urgently required.
Atopic dermatitis is a chronic and recurrent skin disease with severe pruritus, mostly starting in infancy or in early childhood. It is one of the most common skin diseases associated with a family history. Symptoms begin in infancy or childhood, particularly at about 2 months old. Approximately 50% of total atopic dermatitis cases affect children under 2 years old and the most cases affect children under 5 years old. It is very rare for atopic dermatitis to develop in adult stage without a childhood history. In some cases, symptoms may alleviate or disappear as patients grow up. More than 50% of children with atopic dermatitis show improved symptoms after 2 years old.
Atopic dermatitis is characterized by morphology and distribution of skin lesion and is accompanied by pruritus (itchiness), xeroderma and characteristic eczema. Atopic dermatitis starts with eczema in the face, arms and legs in early childhood, but as children grow, atopic dermatitis is observed as eczema in front of the elbows and behind the knees. Lichenification (thickening of skin fold) progress in adult patients and eczema often occurs in the face, chest, neck in addition to legs and arms, which is comparable with infants and young children.
Atopic skin disease usually accompanies other allergic reaction(s). Atopic dermatitis is not only a skin disease but also a signal of allergic march, such as allergic asthma or rhinitis. The initiation and pathogenesis of atopic dermatitis, however, has not yet been well defined. For this reason, a medication that can completely cure atopic dermatitis has not yet been developed.
At present, anti-histamines, steroids or immunomodulators have been used for treating atopic dermatitis. However, when the medication dosage is reduced or administration is stopped, symptoms usually recur. Furthermore, a long-term administration may incur systemic side effects such as hypoadrenocorticism, diabetes, peptic ulcer, hirsutism, alopecia, pigmentation and cataract (especially in infants). The steroid ointments frequently incur serious side effects such as skin atrophy, facial flushing caused by prominent capillaries and folliculitis, etc. Elidel (pimecrolimus) cream and Protopic (tacrolimus, FK506) ointment were developed to replace steroid ointments. Since these medications show no side effects shown by steroid ointments even though they are applied for a long time, the market of these drugs has grown rapidly, accounting 30% of the atopic dermatitis market. However, it was suggested that calcineurin inhibitor might cause cancer. For this reason, only a low dosage of calcineurin inhibitor is allowed for patients under 16 years old. Administration of calcineurin inhibitor is not allowed for an infant under 2 years old. Because of the carcinogenesis of the drugs, market size has drastically decreased.
Anti-histamines may be used to control pruritus. An ultraviolet treatment and an interferon treatment also have been used in some cases. However, in most cases, symptoms are relieved only for a short time and recurred when the administration is stopped. Thus, the atopy is considered as an incurable disease currently. This is why there is an urgent need to develop new drugs to treat and prevent atopy with better efficacy and less side effects than current medicines.
The inventors of the present invention have found that a composition containing a GPCR19 agonist, specifically sodium taurodeoxycholate (HY2191) and its derivatives, is considerably effective in treating atopic dermatitis. The present invention suggests the pharmaceutical compound containing the GPCR19 agonist is useful for preventing, treating and improving atopic dermatitis. Until now, not a single example has been provided for the application of the composition containing sodium taurodeoxycholate (HY2191) and its derivatives in improving, preventing and treating atopic dermatitis. Furthermore, its effectiveness on atopy has neither been reported.